The goal of the proposal is to assess the teratogenic effects of marijuana on the developing nervous system. Marijuana is the most commonly used illicit drug by pregnant women. Its major psychoactive constituent, THC, crosses the placenta and accumulates in fetal brain, potentially harming CNS development, marijuana use in early pregnancy is associated with miscarriage and cognitive abnormalities at age 10 in the offspring, such as lower IQ and learning disabilities, memory impairment and ADHD. Animal models show that THC exposure at a period corresponding to weeks two-three of human pregnancy, results in teratogenesis of the developing nervous system. At this time point, most women are unaware of their pregnancy, and thus of the potentially harmful effects of marijuana. We propose to use a combination of microsurgical, pharmacological and molecular approaches using chick as an animal model, to characterize the embryotoxic effects of marijuana on the initial steps of brain development. This research will provide information for a better understanding of the risks of marijuana exposure during early pregnancy, and will serve as a basis for teratogenic studies involving other drugs of abuse, such as alcohol, cocaine, metamphetamine and opiates, or combinations thereof. [unreadable] [unreadable] [unreadable]